Cell Preservation Services Inc. (CPSI) is a biotechnology corporation focused on developing new and innovative approaches to the use of chilling and freezing temperatures in support of the cell therapy and cancer arenas. In the former, CPSI studies stress pathways activated during hypothermic storage (4C) and cryopreservation (-196) so that improved processes can be developed. Similar data on stress pathways are also being used to potentiate cell death in cancer cells during ablative freezing processes - a regime that couples traditional cryosurgery with adjuvant (e.g. 5-FU, cisplatin) treatments. This approach has recently led to the initiation of a physician sponsored IND for the treatment of advanced stage prostate cancer. This Phase I project proposes to develop a novel therapeutic device (Neuprosol") for the protection of the neural vascular bundles (NVB) and ultimately erectile function during the cryosurgical treatment of prostate cancer. The reasoning behind the development of the device are as follows: (1) NeuprosolTM will be applied directly to the NVB at the time of the cryosurgical application; (2) The protective agents will be designed through molecular analysis to be nerve cell specific; (3) The agents will also be developed to provide varying levels of zonal (thermal) protection; (4) The utilization of this device will be an effective nerve-sparing agents and may also eventually be applied for urethral protection. The Specific Aims of the Phase 1 are: SA1 Determine the effects of freezing on nerve cell viability; SA2 Determine the role played by apoptosis in freezing-induced cell death of neuronal cells; SA3 Determine which novel agents can be used to protect nerve cells from the destructive mechanisms of freezing; SA4 Test the efficacy of NeuprosolTM as a nerve-sparing concept using a canine cryosurgical model. Successful completion of Phase I and 2 will lead to the development of NeuprosolTM which can then be used as an effective nerve-sparing agent during cryosurgical ablation of prostate cancer. Once developed and tested, NeuprosolTM may become useful as a nerve-sparing treatment as well as an alternative method for protecting other tissues, such as the urethra. Consequently, this novel therapeutic design will provide a major benefit to the clinical area as well as provide a platform for future development of therapeutic strategies for the treatment of cancer. [unreadable] [unreadable] [unreadable]